Population-specific evolution of HIV Gag epitopes in genetically diverged patients

Syed H. Abidi, Aga Khan University
Aniqa Shahid, Aga Khan University
Laila S. Lakhani, Aga Khan University
Muhammad R. Khanani, Aga Khan University
Peter Ojwang, Aga Khan University
Nancy Okinda, Aga Khan University
Reena Shah, Aga Khan University
Farhat Abbas, Aga Khan University
Sarah Rowland-Jones, Oxford University
Syed Ali, Aga Khan University

Abstract

Background:

In the microbial ecosystem, microbes compete for space and nutrients. Consequently, some have

developed the ability to kill or inhibit the growth of other competing microbes by producing antimicrobial

substances. As the

‘producer’

species are generally immune to these substances, their compounds act on the

competing microbial species and give the producer more space and access to nutrients for growth. Many currently

used antibiotics were developed by exploiting this potential of certain microbes.

Findings:

Here, the free-living amoeba, Acanthamoeba castellanii

, was investigated for its antibacterial activity

against representative Gram positive and Gram negative bacteria, while bacterial isolates were tested for their

anti-amoebic properties. Conditioned medium from

A. castellanii

showed remarkable bactericidal properties against

methicillin-resistant

Staphylococcus aureus

(MRSA) exhibiting almost 100% kill rate, but had limited effect against

Acinetobacter

sp., Pseudomonas aeruginosa and vancomycin-resistant Enterococcus faecalis

(VRE). Similarly, the

conditioned medium of

E. coli K1 and Enterobacter

sp., exhibited potent anti-Acanthamoebic effects in a concentrationdependent

manner. Conditioned media of

Acanthamoeba, E. coli K1 and Enterobacter

sp. showed no cytotoxicity

in vitro

when tested against human brain microvascular endothelial cells. Active molecule/s in aforementioned amoebic

and two bacterial conditioned media were 5

10 kDa, and <5 kDa>respectively.

Conclusions:

A. castellanii

conditioned medium showed potent bactericidal properties against MRSA. The active

molecule(s) are heat- and pronase-resistant, and in the 5 to 10 kDa molecular mass range. Contrary to this,

E. coli

K1

and

Enterobacter

sp., conditioned medium showed anti-amoebic effects that are <5 kDa in molecular>mass, suggestive

of active metabolites.